title: Experimental confirmation of new drug-target interactions predicted by Drug Profile Matching.
abstract: We recently introduced Drug Profile Matching (DPM), a novel affinity fingerprinting-based in silico drug repositioning approach. DPM is able to quantitatively predict the complete effect profiles of compounds via probability scores. In the present work, in order to investigate the predictive power of DPM, three effect categories, namely, angiotensin-converting enzyme inhibitor, cyclooxygenase inhibitor, and dopamine agent, were selected and predictions were verified by literature analysis as well as experimentally. A total of 72% of the newly predicted and tested dopaminergic compounds were confirmed by tests on D1 and D2 expressing cell cultures. 33% and 23% of the ACE and COX inhibitory predictions were confirmed by in vitro tests, respectively. Dose-dependent inhibition curves were measured for seven drugs, and their inhibitory constants (Ki) were determined. Our study overall demonstrates that DPM is an effective approach to reveal novel drug-target pairs that may result in repositioning these drugs.
authors.affiliation: Department of Biochemistry, Institute of Biology, Eötvös Loránd University , Pázmány Péter sétány 1/C, H-1117 Budapest, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Végner
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Peragovics
authors.forename: László
authors.initials: L
authors.lastname: Tombor
authors.forename: Balázs
authors.initials: B
authors.lastname: Jelinek
authors.forename: Pál
authors.initials: P
authors.lastname: Czobor
authors.forename: Andreas
authors.initials: A
authors.lastname: Bender
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Simon
authors.forename: András
authors.initials: A
authors.lastname: Málnási-Csizmadia
mesh_terms: D000465:Algorithms; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D003412:Cricetulus; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008968:Molecular Conformation; D058990:Molecular Targeted Therapy; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors; D017448:Receptors, Dopamine D2 / Q000819:agonists; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D016861:Cyclooxygenase Inhibitors; C583260:DRD1 protein, human; C581293:DRD2 protein, human; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D007703:Peptidyl-Dipeptidase A